The neurotransmitter dopamine is a key component of the limbic sysem, which plays a critical role in emotional processing, learning and memory, and reward processing.  Disruptions in dopamine synthesis, release, and reuptake underlie many neurological disorders, learning deficits, and diseases.  Previous work from our lab established the importance of the glutamatergic NMDA (N-methyl-D-aspartate) receptor in maintaining normal phasic activity in dopamine neurons of the ventral tegmental area (VTA) and showed that mutations of this receptor cause deficits in fear-related learning, highlighting the importance of dopamine in fear-related learning.  In this project we use in-vivo electrophysiology to record from dopamine neurons of the VTA during Pavlovian fear conditioning.  The paradigm consists of two types of trials where one cue (CS+) is paired with a mild footshock (0.3mA, 0.5 sec), while the other trials utilize a cue (CS-) which predicts the absence of a footshock.  Our preliminary data show plastic differences in neuronal activity patterns across training days associated with both conditioned and unconditioned stimuli, where initially there is increased activity in response to the fearful stimulus, but across days of conditioning, this response shifts to being associated with the conditioned stimulus.

The amygdala, specifically the basolateral amygdala (BLA), has been implicated in fear-related processing and learning and is known to receive domaminergic input from the midbrain, although the specific nature of these connections is unclear. Mutations in functional glutamatergic NMDA receptors have previously been shown to impair phasic dopamine activity, leading to hindered fear-related learning and an onset of anxiety-like phenotypes following fear conditioning. To investigate how phasic dopamine activity modulates neuronal signaling in the BLA , I implanted mice with (controls) and without (KOs) a functional NMDA receptors in dopamine neurons with electrode microdrives bilaterally targeting the BLA and used in vivo electrophysiology to record neuronal activity during fear conditioning. The fear conditioning paradigm consists of 10 CS+ trials with a 10 second cue associated with a 0.3mA, 0.5 second foot shock and 10 CS- trials with a pulsed cue predicting the absence of a foot shock for a total of 20 trials in each session. Preliminary results show that the magnitude of the neuronal response to the unconditioned stimulus changes across days in the controls, while remaining constant in the KOs and that the KOs seem to show differences in tonic levels of activation during the trials compared to the controls. These results suggest that dopamine plays a role in modulating tonic activity in the BLA which may be implicated in influencing fear and anxiety related states.